Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma (Expression)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37992 | GEO | 2013/05/22
SECONDARY ACCESSION(S): PRJNA167212
REPOSITORIES: GEO
Similar Datasets
Project description:Global gene expression analysis of inflammatory leiomyosarcoma (ILMS) and conventional leiomyosarcoma (LMS). RNA was extracted from frozen tumor biopsies (3 ILMS and 15 LMS) and hybridized onto Affymetrix Human Gene 1.0 ST arrays. LMS_18b is the same sample as LMS_18a, analyzed at a different time point. LMS_18b data are not included in the final gene expression analysis; and therefore, there is no Sample data table. This sample was instead used in a previous analysis to show that a normalization method (the ComBat algorithm) was successful in removing batch effects and keeping biological variation.
2013-05-22 | E-GEOD-37992 | biostudies-arrayexpress
Project description:Inflammatory leiomyosarcoma (ILMS) is a soft tissue tumor that morphologically resembles conventional leiomyosarcoma (LMS) admixed with a prominent inflammatory infiltrate. Genetic data on ILMS are still limited but have suggested that this entity is characterized by hyperhaploidy (24-34 chromosomes). This low chromosome number is otherwise uncommon in neoplasia and has been found only in 0.2-0.3% of cytogenetically investigated tumors. Here, three ILMS were investigated using cytogenetic, SNP array and global gene expression analyses. All cases displayed a hyperhaploid origin. Combined with previously reported cases, hyperhaploidy has been found in six of seven cytogenetically investigated ILMS. The copy number distribution of individual chromosomes is clearly nonrandom; the hyperhaploid clones of all six cases displayed disomy for chromosomes 5 and 20, and two copies of chromosomes 18, 21 and 22 were also common. All chromosomes identified as disomic showed a biparental origin by SNP array analysis; whether this is of pathogenetic importance is not known. Compared with conventional LMS, ILMS had a distinct gene expression signature. Furthermore, the number of chromosome copies correlated well with gene expression levels, a finding which has not previously been reported for hyperhaploid tumors. Genes on disomic chromosomes showed higher expression levels in ILMS compared to LMS and disomic chromosomes showed higher average gene expression levels than monosomic chromosomes. Taken together, our findings suggest that disomy for some chromosomes, notably 5 and 20, as well as distorted gene expression balance achieved through massive loss of other chromosomes are essential for the development of ILMS. Tumor DNA was hybridized onto Illumina Human CNV370-Quad v3_C (case 1) and Illumina Human CNV370 v1_C (cases 2 and 3) BeadChips, containing ~370,000 markers, following standard protocols supplied by the manufacturer (Illumina). Data analysis was performed using the GenomeStudio software (Illumina), detecting imbalances by visual inspection.
2013-05-22 | E-GEOD-38015 | biostudies-arrayexpress
Project description:Inflammatory leiomyosarcoma (ILMS) is a soft tissue tumor that morphologically resembles conventional leiomyosarcoma (LMS) admixed with a prominent inflammatory infiltrate. Genetic data on ILMS are still limited but have suggested that this entity is characterized by hyperhaploidy (24-34 chromosomes). This low chromosome number is otherwise uncommon in neoplasia and has been found only in 0.2-0.3% of cytogenetically investigated tumors. Here, three ILMS were investigated using cytogenetic, SNP array and global gene expression analyses. All cases displayed a hyperhaploid origin. Combined with previously reported cases, hyperhaploidy has been found in six of seven cytogenetically investigated ILMS. The copy number distribution of individual chromosomes is clearly nonrandom; the hyperhaploid clones of all six cases displayed disomy for chromosomes 5 and 20, and two copies of chromosomes 18, 21 and 22 were also common. All chromosomes identified as disomic showed a biparental origin by SNP array analysis; whether this is of pathogenetic importance is not known. Compared with conventional LMS, ILMS had a distinct gene expression signature. Furthermore, the number of chromosome copies correlated well with gene expression levels, a finding which has not previously been reported for hyperhaploid tumors. Genes on disomic chromosomes showed higher expression levels in ILMS compared to LMS and disomic chromosomes showed higher average gene expression levels than monosomic chromosomes. Taken together, our findings suggest that disomy for some chromosomes, notably 5 and 20, as well as distorted gene expression balance achieved through massive loss of other chromosomes are essential for the development of ILMS.
2013-05-22 | GSE38015 | GEO
Project description:Leiomyosarcoma (LMS) is a mesenchymal neoplasm with complex copy number alterations and characteristic loss of tumor suppressor genes without known recurrent activating mutations. Clinical management of advanced LMS relies on chemotherapy and complementary palliative approaches, and research efforts to date have had limited success identifying clinically actionable biomarkers or targeted therapeutic vulnerabilities. To explore the biological underpinning of LMS, we evaluated gene expression patterns of this disease in comparison to diverse sarcomas, non-mesenchymal neoplasms and normal myogenic tissues. We identified a recurrent gene expression program in LMS, with evidence of oncogenic evolution of an underlying smooth muscle lineage-derived program characterized by activation of E2F1 and downstream effectors. Recurrently amplified or highly expressed genes in LMS were identified that may represent therapeutic vulnerabilities, including targeting of IGF1R and retinoid signaling pathways. Though the majority of expressed transcripts were conserved across LMS samples, three separate subtypes were identified that were enriched for muscle-associated transcripts (conventional-LMS), immune markers (inflammatory-LMS) or a uterine-like gene expression program (uterogenic-LMS). Each of these subtypes express a unique subset of genes that may be useful in the managemeny of LMS: IGF1R was enriched in conventional LMS with prognostic implications, worse disease-specific survival was observed in inflammatory LMS, and prolactin was elaborated by uterogenic LMS and may represent a disease biomarker. These results extend our understanding of LMS biology and identify several strategies and challenges for further translational investigation.
2020-06-09 | GSE146360 | GEO
Project description:Inflammatory leiomyosarcoma (ILMS) is a soft tissue tumor that morphologically resembles conventional leiomyosarcoma (LMS) admixed with a prominent inflammatory infiltrate. Genetic data on ILMS are still limited but have suggested that this entity is characterized by hyperhaploidy (24-34 chromosomes). This low chromosome number is otherwise uncommon in neoplasia and has been found only in 0.2% to 0.3% of cytogenetically investigated tumors. Here, three ILMS were investigated using cytogenetic, single-nucleotide polymorphism (SNP) array, and global gene expression analyses. All cases displayed a hyperhaploid origin. Combined with previously reported cases, hyperhaploidy has been found in six of seven cytogenetically investigated ILMS. The copy number distribution of individual chromosomes is clearly nonrandom; the hyperhaploid clones of all six cases displayed disomy for chromosomes 5 and 20, and two copies of chromosomes 18, 21, and 22 were also common. All chromosomes identified as disomic showed a biparental origin by SNP array analysis; whether this is of pathogenetic importance is not known. Compared with conventional LMS, ILMS had a distinct gene expression signature. Furthermore, the number of chromosome copies correlated well with gene expression levels; disomic chromosomes showed higher gene expression levels than monosomic chromosomes, a finding that has not previously been reported for hyperhaploid tumors. Taken together, our findings suggest that disomy for some chromosomes, notably 5 and 20, as well as distorted gene expression achieved through massive loss of other chromosomes are essential features of ILMS.
| S-EPMC3459276 | biostudies-literature
Project description:Leiomyosarcoma (LMS) is a mesenchymal neoplasm with complex copy number alterations and characteristic loss of tumor suppressor genes without known recurrent activating oncogenic mutations. Clinical management of advanced LMS relies on cytotoxic chemotherapy and complementary palliative approaches, and research efforts to date have had limited success identifying clinically actionable biomarkers or targeted therapeutic vulnerabilities. To explore the distinctive biological underpinning of LMS, we evaluated gene expression patterns of LMS cell lines and correlated results with primary tumor samples.
2020-01-22 | GSE143968 | GEO
Project description:Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation, and there are three molecular subtypes of LMS which have been defined previously by our lab. To further validate these subtypes and identify potential therapeutic targets in each subtype, we profiled the LMS cases from each subtype with RNA-Seq technology.
2015-12-25 | GSE62544 | GEO
Project description:Background: Undifferentiated pleomorphic sarcoma (UPS), used to be called malignant fibrous histiocytoma (MFH), is a malignant soft tissue tumor of uncertain origin, and is characterized by morphology. UPS often share similar morphological characters with other sarcomas, especially Leiomyosarcoma. Leiomyosarcoma (LMS) is another malignant soft tissue sarcoma with complex genomic abnormalities, origin from smooth muscle. As a result, development of gene signature and/or biomarkers distinguishing UPS and LMS will definitely help the pathologist to precisely diagnose those patients. However, in the past, UPS was reported to be indistinguishable with LMS by genomic profiles. Methods and Results: In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. Overall, UPS was undistinguished with LMS by 3SEQ data, however, when we stratified LMS into three subtypes, UPS was shown to share similar expression pattern with Subtype II LMS, but had distinct molecular expression patterns with Subtype I and Subtype III LMS. Additional Immunohistochemistry staining by using LMS Subtype I and Subtype II markers validated that UPSs were positive for Subtype II marker ARL4C, but negative for Subtype I marker LMOD1. Furthermore, CD4 was shown to be significantly more highly expressed in UPS than LMS in both mRNA and protein levels. Conclusion: This study first reported that UPS shared similar gene expression pattern with subtype II LMS and UPS recapitulated the expression profiles of subtype II LMS.
2015-05-19 | GSE53844 | GEO
Project description:Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for LMS. We demonstrate the existence of 3 molecular subtypes in a cohort of 99 cases and an independent cohort of 82 LMS. Two new FFPE tissue-compatible diagnostic immunohistochemical markers are identified: LMOD1 for subtype I LMS and ARL4C for subtype II LMS. Subtype I and subtype II LMS are associated with good and poor prognosis, respectively. The LMS subtypes show significant differences in expression levels for genes for which novel targeted therapies are being developed.
2015-05-19 | GSE45510 | GEO
Project description:Leiomyosarcoma (LMS) is a malignant neoplasm of smooth muscle and is an aggressive soft tissue tumor, have complex genetic abnormalities and could be defined as three molecular subtypes. Since that the molecular heterogeneity of LMS, the pathogenesis analysis per subtype will be highly necessary and helpful to understand the etiology of this more common sarcoma.
2015-05-19 | GSE54511 | GEO